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BioMed Research International
Volume 2014 (2014), Article ID 686505, 16 pages
http://dx.doi.org/10.1155/2014/686505
Research Article

Network Analysis of Neurodegenerative Disease Highlights a Role of Toll-Like Receptor Signaling

1The Microsoft Research, University of Trento Centre for Computational Systems Biology (COSBI), Piazza Manifattura 1, 38068 Rovereto, Italy
2Department of Mathematics, University of Trento, Via Sommarive, 14-38123 Povo, Italy

Received 5 September 2013; Revised 20 November 2013; Accepted 30 November 2013; Published 16 January 2014

Academic Editor: Stavros J. Hamodrakas

Copyright © 2014 Thanh-Phuong Nguyen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Despite significant advances in the study of the molecular mechanisms altered in the development and progression of neurodegenerative diseases (NDs), the etiology is still enigmatic and the distinctions between diseases are not always entirely clear. We present an efficient computational method based on protein-protein interaction network (PPI) to model the functional network of NDs. The aim of this work is fourfold: (i) reconstruction of a PPI network relating to the NDs, (ii) construction of an association network between diseases based on proximity in the disease PPI network, (iii) quantification of disease associations, and (iv) inference of potential molecular mechanism involved in the diseases. The functional links of diseases not only showed overlap with the traditional classification in clinical settings, but also offered new insight into connections between diseases with limited clinical overlap. To gain an expanded view of the molecular mechanisms involved in NDs, both direct and indirect connector proteins were investigated. The method uncovered molecular relationships that are in common apparently distinct diseases and provided important insight into the molecular networks implicated in disease pathogenesis. In particular, the current analysis highlighted the Toll-like receptor signaling pathway as a potential candidate pathway to be targeted by therapy in neurodegeneration.